Recombinant HCMV and RHCMV vectors and uses thereof
AssigneeOregon Health & Science University
InventorsLouis Picker, Jay A. Nelson, Klaus Frueh, Michael A. Jarvis, Scott G. Hansen
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Abstract
The recombinant rhesus cytomegalovirus (RhCMV) and human cytomegalovirus (HCMV) vectors of this invention encode heterologous antigens, such as pathogen-specific antigens or tumor antigens, which may be used, for example, for the treatment or prevention of infectious disease or cancer. The recombinant RhCMV or HCMV vectors elicit and maintain high level cellular immune responses specific for the heterologous antigen while including deletions in one or more genes essential or augmenting for CMV replication, dissemination or spread.
Claims54
A method of treating a subject with an infectious disease or cancer comprising administering to the subject in need thereof a recombinant viral vector comprising a nucleic acid sequence encoding a human cytomegalovirus (HCMV) or rhesus cytomegalovirus (RhCMV) backbone vector and at least one heterologous antigen,
- wherein the at least one heterologous antigen is a pathogen-specific antigen or a tumor antigen, and
- wherein the recombinant viral vector:
- (a) comprises a deletion in the HCMV UL82 or RhCMV Rh110 gene that eliminates expression of a functional pp71 protein, (b) is deficient in host to host spread, (c) infects a HCMV or RhCMV seropositive host upon administration of said recombinant viral vector, and (d) induces and maintains a long-term effector memory T cell response to the at least one heterologous antigen in the seropositive host.
A method of treating a subject infected with human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) comprising administering to the subject in need thereof a recombinant viral vector comprising a nucleic acid sequence encoding a HCMV or RhCMV backbone vector and at least one HIV-derived or SIV-derived antigen,
- wherein the recombinant viral vector:
- (a) comprises a deletion in the HCMV UL82 or RhCMV Rh110 gene that eliminates expression of a functional pp71 protein, (b) is deficient in host to host spread, (c) infects a HCMV or RhCMV seropositive host upon administration of said recombinant viral vector, and (d) induces and maintains a long-term effector memory T cell response to the at least one HIV-derived or SIV-derived antigen in the seropositive host.
A method of inducing a tumor-specific or pathogen-specific immune response in a subject at risk of developing cancer or becoming infected with an infectious disease comprising administering to the subject in need thereof a recombinant viral vector comprising a nucleic acid sequence encoding a HCMV or RhCMV backbone vector and at least one heterologous antigen,
- wherein the at least one heterologous antigen is a tumor antigen or a pathogen-specific antigen, and
- wherein the recombinant viral vector:
- (a) comprises a deletion in the HCMV UL82 or RhCMV Rh110 gene that eliminates expression of a functional pp71 protein, (b) is deficient in host to host spread, (c) infects a HCMV or RhCMV seropositive host upon administration of said recombinant viral vector, and (d) induces and maintains a long-term effector memory T cell response to the at least one heterologous antigen in the seropositive host.
A method of inducing an HIV-specific or SIV-specific immune response in a subject at risk of becoming infected with HIV or SIV comprising administering to the subject in need thereof a recombinant viral vector comprising a nucleic acid sequence encoding a HCMV or RhCMV backbone vector and at least one HIV-derived or SIV-derived antigen,
- wherein the recombinant viral vector:
- (a) comprises a deletion in the HCMV UL82 or RhCMV Rh110 gene that eliminates expression of a functional pp71 protein, (b) is deficient in host to host spread, (c) infects a HCMV or RhCMV seropositive host upon administration of the recombinant viral vector, and (d) induces and maintains a long-term effector memory T cell response to the at least one HIV-derived or SIV-derived antigen in the seropositive host.
Dependencies are inferred from the claim text.